There are several components of the research program. Component 1: Platelet Biology, Reactivity and Genomics. Utilizing one of the largest human samples (FHS: Framingham Heart Study) with platelet reactivity we have conducted deeper genetic scans for contributing genes. These scans use new genetic maps with deeper coverage of rare variation. DNA genotyping of an additional diverse population sample, the FHS OMNI cohort, was supported allowing additional validation samples and gene coverage for platelet reactivity traits. Further support was provided for genotyping of the U.K.-based Caerphilly Study in Men cohort, a rich study repository of hemostatic factor and platelet reactivity trait data. New genetic studies in 2015-16 led by the lab expanded the SNP platforms and imputation used to study platelet traits. A large effort to study the genetics of PLT (platelet count) and MPV (mean platelet volume) in up to >155,000 individuals had yielded many new gene discoveries and was led by my lab (Eicher et al., 2016 AJHG). A separate Exome Sequencing based study led to new discoveries in relation to platelet reactivity (Eicher et al., in review). Targeted qPCR RNA measurements in FHS platelet samples are also completed and underway to investigate mechanistic questions for specific candidate genes. A major initiative in the lab is large-scale platelet data collection in the FHS Gen3/Omni2 Exam 3. Deep data collection was started in April 2016 and data on 625 sample will have completed by the end of the Fiscal Year. Completion of the study is anticipated in 2019. Component 2: Tissue-specific Gene Expression. A major cell- and tissue-specific database of genetic factors on gene expression (eQTLs) was maintained and updated. This catalog was used to add information on genes to many disease and risk factor studies, primarily in the cardiovascular and metabolic disease domains. A major study was undertaken to integrate FHS gene expression data with data on 15,000 other samples. This led the identification and validation of >1,200 genes whose RNA levels change during aging published in the last Fiscal Year (Peters et al., 2015 Nat Comm). Research was supported to conduct experiments knocking out some of these novel genes in the worm C. elegans and D. melanogaster in order to assess whether they significantly affect lifespan. Component 3: Development and Application of Bioinformatics Resources. Beyond the eQTL database mentioned above, a large genome-wide association study (GWAS) results database GRASP was updated, and an online NIH query site developed. The database is publicly downloadable and queryable at the URL: grasp.nhlbi.nih.gov/Overview.aspx. This database of results was expanded in early FY15 to 2,100 GWAS articles and is undergoing an additional expansion in FY16 to >2,900 articles. The database was widely used in addressing many research questions as evidenced by thousands of web hits and queries per month and citations to related publications.